Monday 26 June 2017

Prevention and treatment of homocysteine

Elevated homocysteine is a greater risk factor for developing cardiovascular disease than cholesterol. This risk can be reduced through the diet and supplementation with vitamins B6, B12 and folic acid. But which diet is best? And what quantities of supplements should be given?


At high doses, homocysteine is a toxic metabolic product of the amino acid methionine and is a powerful initiator of free radical reactions. The discovery of the role that this substance plays in our body is considered to be one of the most important clinical findings of the past ten years.


Greater risk factor than cholesterol

The cholesterol hypothesis states that people with elevated cholesterol are at a higher risk of developing cardiovascular disease. However, a review of several studies involving a total of 68,000 people revealed that the ‘bad’ LDL cholesterol is actually not so bad at all [3]. According to the researchers, in all studies either no link was found in elderly people between elevated LDL cholesterol and cardiovascular diseases, or that the link was inversely proportional. The latter means that LDL cholesterol can also be healthy; according to the researchers, it could even protect against Parkinson’s and Alzheimer’s disease. Homocysteine paints a different story.


More so than cholesterol, elevated homocysteine was found to be an important risk factor in the development of cardiovascular diseases [1,4]. There is increasing scientific evidence that homocysteine can damage the blood vessel wall and therefore can give rise to plaque formation and reduced elasticity of the blood vessels, thus obstructing the blood flow. Homocysteine may also increase the stickiness of blood platelets. Over time, this can result in, for example, a cardiac infarction or stroke. Other diseases, such as neural tube defects [2], mental decline in the elderly (dementia) and rheumatoid arthritis have also been linked to elevated homocysteine levels.


Impaired homocysteine metabolism

In many people, homocysteine metabolism is impaired, allowing homocysteine to accumulate. It is estimated that 9% of the population and approximately 20% of patients with cardiovascular problems suffer from a genetic disorder which prevents homocysteine from being broken down properly [5]. These people therefore have significantly elevated levels of homocysteine in the blood. But of equal importance is that relative deficiencies of vitamin B6, vitamin B12 and especially folic acid can significantly increase homocysteine levels.


Vitamins B6, B12 and folic acid are substances that are essential for normalising elevated homocysteine levels. These three B vitamins all play an important role in so-called methylation reactions in the body, an important biochemical process where a methyl group (-CH3) is transferred. In this process, folic acid and vitamin B12 provide the required methyl groups. The reversion of methionine from the harmful homocysteine is a key example of a methylation reaction. But also for many other important reactions in the body, such as the synthesis of neurotransmitters and DNA synthesis, properly functioning methylation is essential.


Food rich in B vitamins

The approach always starts with the diet. Our Palaeolithic diet consisted of vitamin B-rich plants, fruit, nuts, fish, molluscs and shellfish and, when available, meat. Our present-day diet mainly consists of processed and red meat (which is rich in B12), margarine, dairy products, refined grains and sugars. Furthermore, the micronutrients have largely disappeared from this high-energy and easy to digest food. This is where there is a link with the vitamin deficiencies commonly seen in the Western world, as well as the ‘civilisation’ diseases we are contending with, such as cardiovascular disease.


As well as the Palaeolithic diet, the Mediterranean diet is associated with elevated vitamin and mineral levels in the body [6]. The Mediterranean diet consists of fruit, vegetables, complex carbohydrates, olive oil, red wine, fish and white meat. Like the Palaeolithic diet, it also provides more B vitamins than the average Western diet. These B vitamins contribute to lower homocysteine levels.


What quantities should be supplemented?

When homocysteine levels are too high, the Nutrition Committee of the American Heart Association recommends supplementing 2.5 mg of folic acid, 0.5 mg of vitamin B-12 and 25 mg of vitamin B6. This is in addition to a healthy diet, if available. Therefore, a lot is possible through the diet and supplementation, both from a preventative and curative point of view.



[1] Blacher J, Safar ME. Homocysteine, folic acid, B vitamins and cardiovascular risk. J Nutr Health Aging 2001;5(3):196-9.

[2] Refsum H. Folate, vitamin B12 and homocysteine in relation to birth defects and pregnancy outcome. Br J Nutr 2001 May;85 Suppl 2:S109-13.

[3] Uffe Ravnskov et al., Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review, BMJ Open 2016;6:e010401

[4] Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ 2002 Nov 23;325(7374):1202.